Garnett, M. | bioRxiv Science

bioRxiv2018

JACKS: joint analysis of CRISPR/Cas9 knock-out screens

Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. Their range of applications remains limited by signal variability from different guide RNAs targeting the same gene, which confounds analysis, and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyses screens performed with the same guide RNA library. Modeling the variable guide efficacies greatly improves hit identification, and allows a 2.5-fold reduction in required cell numbers without sacrificing performance compared to current analysis standards.

genomics↗

bioRxiv2018

Integrative analysis of pharmacogenomics in major cancer cell line databases using CellMinerCDB

As precision medicine demands molecular determinants of drug response, CellMinerCDB provides (https://discover.nci.nih.gov/cellminercdb/) a web-based portal for multiple forms of pharmacological, molecular, and genomic analyses, unifying the richest cancer cell line datasets (NCI-60, NCI-SCLC, Sanger/MGH GDSC, and Broad CCLE/CTRP). CellMinerCDB enables genomic and pharmacological data queries for identifying pharmacogenomic determinants, drug signatures, and gene regulatory networks for researchers without requiring specialized bioinformatics support. It leverages overlaps of cell lines and tested drugs to allow assessment of data reproducibility. It builds on the complementarity and strength of each dataset. A panel of 41 drugs evaluated in parallel in the NCI-60 and GDSC is reported, supporting drug reproducibility across databases, repositioning of bisacodyl and acetalax for triple negative breast cancer, and identifying novel drug response determinants and genomic signatures for topoisomerase inhibitors and schweinfurthins in development. CellMinerCDB also allowed the identification of LIX1L as a novel mesenchymal gene regulating cellular migration and invasiveness.

bioinformatics↗